Indole-3-glycerol phosphate synthase (IGPS) serving as a drug target in M. tuberculosis.

Tuberculosis (TB) is a disease that is caused by a bacteria called Mycobacterium tuberculosis and primarily attacks the lungs but can spread to other areas of the body as well. TB can develop resistance to drugs that may be used to cure the disease. Multi-drug resistant TB, for example, does not respond to the two most powerful anti-TB drugs, which are isoniazid and rifampicin. For this reason, finding new ways to target TB are highly needed. One possible way to do this is to target the enzymes in the tryptophan biosynthetic pathway of M. tuberculosis. Studies have suggested that the enzyme indole-3-glycerol phosphate synthase (IGPS) in M. tuberculosis(MtIGPS) coded for by the trpC gene could be a target (Shen et al. 2009). The interactions between ligands and MtIGPS were thus investigated by introducing mutations to residues that had been proposed to play a role in catalysis or binding. Specifically, E168 was mutated to Q and K119 was mutated to R. Predictions for these mutations were that K119 is a catalytic acid and that E168 plays a role in substrate binding. We investigated the impact of these mutations on steady state kinetics and rate-pH profiles to obtain insights into the roles of these two residues in substrate binding and catalysis. These findings will facilitate the design of MtIGPS inhibitor candidates. © FASEB.

Citation

Maryum Bhatti, Nina Goodey, Sarah Cho, Natalie Jefferson, Patrycja Marin. Indole-3-glycerol phosphate synthase (IGPS) serving as a drug target in M. tuberculosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022 May;36 Suppl 1

PMID: 35552588

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